Hydrazine hydrate (1:1) → 2-(2-{[6-(4-Fluorophenyl)-2-naphthyl]sulfonyl}phenyl)-1,3,4-oxadiazole

HRID 735341Notes

Reaction equation

HRID 735341 reaction equation
O.[NH2:2][NH2:3].[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([S:21]([C:24]2[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]([O:28][CH3:29])=O)(=[O:23])=[O:22])[CH:15]=[CH:14]3)=[CH:7][CH:6]=1>O1CCOCC1>[F:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[CH:12]=[C:13]3[C:18](=[CH:19][CH:20]=2)[CH:17]=[C:16]([S:21]([C:24]2[CH:33]=[CH:32][CH:31]=[CH:30][C:25]=2[C:26]2[O:28][CH:29]=[N:2][N:3]=2)(=[O:23])=[O:22])[CH:15]=[CH:14]3)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 68898972Methyl 2-{[6-(4-fluorophenyl)-2-naphthyl]sulfonyl}benzoate

Product 1

HCID 689003262-(2-{[6-(4-Fluorophenyl)-2-naphthyl]sulfonyl}phenyl)-1,3,4-oxadiazoleYield 51.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

Hydrazine hydrate (2.25 mL, 46 mmol) was added to a solution of methyl 2-{[6-(4-fluorophenyl)-2-naphthyl]sulfonyl}benzoate (Example 38, 0.42 g, 1.0 mmol) in 1,4-dioxane (1 mL), stirred for 1 hour at room temperature then heated at 90° C. overnight. Solvent was removed in vacuo and the residue azeotroped using toluene. Triethyl orthoformate (10 mL) and a catalytic quantity of (±)-10-camphorsulfonic acid were added to the resultant crude hydrazide then stirred and heated at 90° C. overnight. Solvent was removed in vacuo, water (100 mL) added and extracted with ethyl acetate (2×75 mL). Extracts were washed with water and saturated brine then dried (MgSO4), filtered and evaporated to a yellow residue. Purification by flash column chromatography eluting with a 20-60% ethyl acetate/isohexane gradient gave 2-(2-{[6-(4-fluorophenyl)-2-naphthyl]sulfonyl}phenyl)-1,3,4-oxadiazole (0.22 g, 51%). 1H NMR (500 MHz, d6-DMSO) δ 9.46 (1H, s), 8.59 (1H, s), 8.40 (1H, dd, J=1.0, 8.0 Hz), 8.37 (1H, s), 8.30 (1H, d, J=8.7 Hz), 8.20 (1H, d, J=8.8 Hz), 8.05 (1H, dd, J=1.7, 8.6 Hz), 8.00-7.96 (1H, m), 7.93-7.91 (3H, m), 7.87-7.85 (2H, m), 7.42-7.33 (2H, m); m/z (ES+) 431 [MH+].

Workup

  1. temperaturethen heated at 90° C. overnight
  2. customSolvent was removed in vacuo
  3. customthe residue azeotroped
  4. additionTriethyl orthoformate (10 mL) and a catalytic quantity of (±)-10-camphorsulfonic acid were added to the resultant crude hydrazide
  5. stirringthen stirred
  6. temperatureheated at 90° C. overnight
  7. customSolvent was removed in vacuo, water (100 mL)
  8. additionadded
  9. extractionextracted with ethyl acetate (2×75 mL)
  10. washExtracts were washed with water and saturated brine
  11. dry with materialthen dried (MgSO4)
  12. filtrationfiltered
  13. customevaporated to a yellow residue
  14. customPurification by flash column chromatography
  15. washeluting with a 20-60% ethyl acetate/isohexane gradient

Sources & evidence

ORD record
ord-c95c2f291268429a951501e5ccb1adf9
Source dataset
uspto-grants-2009_09
Patent number
US07592456B2

Reaction notes

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